title: N-methyl-D-aspartate receptors and protein synthesis are necessary for reinstatement of conditioned fear.
abstract: Conditioned fear is extinguished if a conditioned animal receives the conditioned stimulus without an unconditioned stimulus. The extinguished fear response can be reinstated after the animal experiences a mild unconditioned stimulus. Although extensive studies on the neuronal circuitry and neurochemical mechanisms leading to fear acquisition and extinction have been carried out, few studies have focused on reinstatement. In this study, we investigated the effects of N-methyl-D-aspartic acid receptor (NMDAR) antagonists, protein synthesis inhibitors, cannabinoid receptor type 1 (CB1R) antagonists, and benzodiazepine on reinstatement of conditioned fear in mice. An intraperitoneal injection of the NMDAR antagonist MK-801 or the protein synthesis inhibitor anisomycin before the reminder shock attenuated fear reinstatement tested the next day. However, anisomycin had no effect on fear reinstatement tested 2 h after the reminder shock. CB1R antagonists, SR141716, and a benzodiazepine, diazepam, had no effect on fear reinstatement. These results suggested that NMDAR and protein synthesis-dependent plasticity contributed toward the reinstatement of conditioned fear and that protein synthesis was involved in consolidation of reinstated fear.
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Huilian
authors.initials: H
authors.lastname: Shen
authors.forename: Hikaru
authors.initials: H
authors.lastname: Igarashi
authors.forename: Natsuko
authors.initials: N
authors.lastname: Imamura
authors.forename: Norio
authors.initials: N
authors.lastname: Matsuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nomura
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014176:Protein Biosynthesis / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism*
chemical_list: D011500:Protein Synthesis Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D000841:Anisomycin